THE QUANTITATIVE RELATIONSHIPS OF THE PARTITION COEFFICIENTS CALCULATED IN THE SERIES OF N-R-AMINE FUNCTIONAL DERIVATIVES

Using on-line services and the ChemBioOffice2014 software package the values of the partition coefficients of some N-R-amine derivatives have been calculated. To identify the quantitative relationships and select the optimal algorithm of calculations the correlation and regression analysis of the values obtained has been conducted. Statistically significant values of correlation for the partition coefficients calculated have been determined. It has been shown that it is advisable to use the value AlogPs for further application.

Lipophilicity is one of the criteria for assessing the similarity of synthetic substances and drugs, and it affects the biological activity of substances [9,13,14]. The partition coefficient of n-octanol-water (logP) characterizes physicochemical properties of substances in solutions and is used to simulate their behaviour in the body [3,14]. Distribution and redistribution of substances between lipophilic (fatty) and aqueous phases are part of biological processes, in particular transmembrane transport through lipid layers [11]. Hydrophobicity plays an important role in determining distribution of a substance in the body after absorption, its metabolic rate and elimination. The hydrophobic effect is essential for binding of drugs with their receptors [13].
The ability to predict biological properties of compounds through their lipophilicity allows to optimize the search for new drugs and is often included in equations for calculations of the quantitative structure -activity relationships (QSAR) [16].
The value logP is experimentally determined by the classical method of measuring distribution of organic compounds between the non-polar phase and water [14] using chromatographic [18], electrochemical [23] and other methods.
However, experimental methods to determine logP are time-consuming and expensive, and the values obtained often differ due to the influence of many factors. Therefore, today a significant number of algorithms for theoretical calculations of values logP implemented using the appropriate software [5,6,8,17,24,25].
The values of the partition coefficients of n-octanolwater experimentally obtained with the values theoretically calculated by different algorithms (AlogPs, IAlogP, ClogP, miLogP, logP KowWIN , xlogP3, etc.) were compared for 193 substances [19] and more than 96 000 compounds (including databases of Nykomed and Pfizer) [15]. In both studies the experimental data better correlate with the methods of AlogPs, xlogP3, logP KowWIN .
Attempts to achieve proportionality of results of the theoretical calculation methods of prediction and the experimental determination of lipophilicity of organic compounds are still relevant in modern scientific studies [1, 16,22].
The aim of this work is to determine the mutual correlation of the values of the partition coefficients in the series of some functional derivatives of N-R-amines (1-21) calculated by different algorithms.
In total, the statistical sample included the comparison of 6 values of the partition coefficients calculated for 21 compounds. During the statistical processing of the research results when analysing the sample with the length of 21 cases the values of the Pearson correlation coefficient, which is more than 0.40 (p≤0.05), is considered to be statistically significant [2].
Calculations of correlations of the values of the partition coefficients calculated for compounds 1-21 were performed using the STATISTIKA 8 software [4,21]. According to the requirements of mathematical statistics the correlation coefficient indicates the close relationship between the values: at values less than 0.3 -the relationship is absent, in the range of 0.3-0.7 it is medium, more than 0.7 -it is strong [10,20].

Results and Discussion
As can be seen from Table, almost all compounds are characterized by negative values of the partition coefficients; probably it is due to the presence of the polar moiety -substituted Nitrogen atom in their structure. Increase of numeric values, and hence lipophilicity, is observed in the case of increase in the number of nonpolar substituents (alkyl substituents or the phenyl nucleus in compounds 19-20). Glycine (12), for which the calculated values (excluding logP) agree with the experimental ones [12], and its alkyl substituents (13,16) are characterized by the maximum values of hydrophilicity. It can be also explained by the considerations previously mentioned.
Analysis of the results of statistical processing indicates that the coefficients of lipophilicity calculated by different algorithms for compounds (1-21) correlate (%) with each other in a different way and are statistically significant (Fig. 1-11).
These combinations of the Pearson correlation coefficients and indicators of significance indicate the reliability of the graphs and equations shown in Fig. 1-11.
The position of the curve the values AlogPs theoretically calculated in relation to the results of other calculations of the partition coefficients (Fig. 12) may in-dicate the use of the optimally averaged algorithm of their determination.
Therefore, the results of our study allow to propose the values AlogPs obtained for further application when determining QSAR, as well as the degree of its manifestation among N-R-amine derivatives for planning a targeted search biologically active substances in this series. CONCLUSIONS 1. Using on-line services and the ChemBioOffice2014 software package the values of the partition coefficients of some N-R-amine derivatives have been calculated.
2. To identify the quantitative relationships and select the optimal algorithm of calculations the correlation and regression analysis of the values obtained has been conducted.
3. Statistically significant values of correlation for the partition coefficients calculated have been determined. It has been shown that it is advisable to use the value AlogPs for further application.